MIXED D-2 5-HT2A ANTAGONISM OF AMPHETAMINE-INDUCED FACILITATION OF BRAIN-STIMULATION REWARD/

Recent experiments have demonstrated that 5-HT2A antagonists can modif y electrophysiological, neurochemical, and behavioral responses to psy chostimulants. These findings led to an interest in using 5-HT2A antag onists to block the effects of psychostimulants on brain reward mechan isms. The present experiments assessed the ability of mixed D-2/5-HT2A antagonists to reverse amphetamine-induced facilitation of self-stimu lation. The D-2/5-HT2A antagonists MDL 28,133A and risperidone attenua ted the effects of cocaine and amphetamine, but only at antagonist dos es that elevated baseline self-stimulation thresholds. A comparison of the effects of the mixed antagonists to those of haloperidol and etic lopride revealed that all four antagonists produced similar anti-stimu lant effects when the influence of the drugs on baseline responding wa s considered. The D-2 activity of the antagonists appears to account f or their ability to reduce the effects of psychostimulants on self-sti mulation. 5-HT2A antagonism makes a negligible contribution to the ant i-amphetamine effects.